Associations between breastfeeding intention, breastfeeding practices and post-natal depression during the COVID-19 pandemic: A multi-country cross-sectional study.

Associations between breastfeeding intention, duration and post-natal depression (PND) have been shown in pre-COVID-19 studies. However, studies during COVID-19 have not examined the associations between breastfeeding intention, breastfeeding practices, and PND in an international sample of post-natal women, taking into consideration COVID-19 related factors. This is the first study to address this gap as both PND and breastfeeding may be affected by COVID-19, and have important long-term effects on women's and infant's health. A cross-sectional internet-based survey was conducted with 3253 post-natal women from five countries: Brazil, South Korea, Taiwan, Thailand, and the United Kingdom from July to November 2021. The results showed that women who intended to breastfeed during pregnancy had lower odds of having PND than women who did not intend to. Women who had no breastfeeding intention but actually breastfed had greater odds (AOR 1.75) of having PND than women who intended to breastfeed and actually breastfed. While there was no statistical significance in expressed breast milk feeding in multivariable logistic regression models, women who had shorter duration of breastfeeding directly on breast than they planned had greater odds (AOR 1.58) of having PND than those who breastfed longer than they planned even after adjusting for covariates including COVID-19-related variables. These findings suggested the importance of working with women on their breastfeeding intention. Tailored support is required to ensure women's breastfeeding needs are met and at the same time care for maternal mental health during and beyond the pandemic.

Cytotoxicity of Potassium Salts of (+)- and (-) Usnic Acid for Paramecium caudatum.

We analyzed cytotoxicity of water-soluble potassium salts of (+)- and (-) usnic acid (UA) for ciliates P. caudatum. The median lethal concentrations for (+)- and (-) enantiomers did not significantly differ and were 7.5±0.5 and 6.7±0.4, respectively. In a concentration of 8 µM, (+)-UA and (-)-UA salts increased the content of TBA-reactive products, which indicates the formation of oxidative stress under the action of high UA concentrations. In the presence of (+)-UA and (-)-UA salts in a concentration range from 2 to 8 µM, the number of food vacuoles in ciliates decreased, which attested to a decrease in phagocytosis activity. The concentrations of UA enantiomers >0.5 µM affected macronucleus morphology (shape and size). The cytotoxic activity of (+)-UA and (-)-UA salts against P. caudatum did not differ.

The importance of both CYP2C19 and CYP2B6 germline variations in cyclophosphamide pharmacokinetics and clinical outcomes.

Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug, it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for the role of germline pharmacogenetic variation in both plasma pharmacokinetics and clinical outcomes. There is a substantial indication from 13 pharmacokinetic and 17 therapeutic outcome studies, in contexts as diverse as haematological malignancy, breast cancer, systemic lupus erythematosus and myeloablation, that pharmacogenetic variation in both CYP2C19 and CYP2B6 influence the bioactivation of cyclophosphamide. An additional role for pharmacogenetic variation in ALDH1A1 has also been reported. Future studies should comprehensively assess these 3 pharmacogenes and undertake appropriate statistical analysis of gene-gene interactions to confirm these findings and may allow personalised treatment regimens.

Bone micro-architecture of elite alpine skiers is not reflected by bone mineral density.

UNLABELLED: Bone quality is affected by muscle forces and external forces. We investigated how micro-architecture is influenced in elite alpine skiers who have received high loading levels throughout their adolescent bone development. Bone strength was higher in skiers, likely due to external forces, but muscle forces may also be a significant contributor. INTRODUCTION: Impact loading and muscle forces affect bone quality, but little is known about how they influence 3 dimensional aspects of bone structure. This study investigated bone quality in female and male elite alpine skiers using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: HR-pQCT at the distal radius and tibia, whole-body lean mass, and muscle strength were assessed in 10 female (22.7 ± 3.9 years) and 12 male (25.5 ± 3.3 years) Canadian national alpine team athletes and compared to recreationally active female (N = 10, 23.8 ± 3.2 years) and male (N = 12; 23.7 ± 3.6 years) control subjects. HR-pQCT standard parameters and customized cortical and finite element (FE) analyses were performed and analyzed using one-way ANOVA and Pearson's correlation. RESULTS: Male and female skiers had stronger bones than controls at radius (38-49 %, p < 0.001) and tibia (24-28 %, p < 0.001). This result was not consistently reflected by total bone mineral density (BMD) because higher trabecular BMD occurred in parallel with lower cortical BMD, which was due to a redistribution of mineral leading to a shift of the endocortical margin toward a thicker cortex. The endocortical regional adaptation was likely responsible for the greater strength of the athletes' bones. Lean mass and muscle strength was 29 to 90 % greater (p < 0.001) in athletes compared to controls. Good associations between muscle strength and FE-estimated bone strength were found (r = 0.63 to 0.80; p < 0.001), although micro-architecture was more strongly associated with muscle outcomes in females than males. CONCLUSIONS: Higher bone strength in elite alpine skiers is achieved through micro-architectural adaptation that is not apparent by BMD measurements alone. The improved micro-architecture at radius and tibia suggests that muscle forces may play an important role in bone adaptation.

Bone micro-architecture, estimated bone strength, and the muscle-bone interaction in elite athletes: an HR-pQCT study.

Athletes participating in sports characterized by specific loading modalities have exhibited different levels of augmentation of bone properties; however, the extent to which these loading environments affect bone micro-architecture and estimated bone strength (i.e., bone quality) remains unclear. Furthermore, the relative role of impact loading versus loading due to muscle forces in determining bone properties is confounded. The objectives of this study were 1) to examine the role of impact loading on bone quality of the distal radius and distal tibia in elite athletes, as determined by high resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA), and 2) to investigate the relationship between bone quality and muscle strength in elite athletes. Ninety-five females (n=59) and males (n=36) between the ages of 16-30 years participated in the study. Participants included alpine skiers (high-impact), soccer players (moderate impact), swimmers (low-impact), and non-athletic controls. All group comparisons were made after accounting for age, height, and body mass. As expected, minimal differences in HR-pQCT parameters across groups were observed at the non weight-bearing distal radius. At the weight-bearing distal tibia, female alpine skiers and soccer players had significantly higher bone density, cortical thickness, and failure load (i.e., bone strength (N) in compression estimated by FEA) than swimmers (p<0.05). Female alpine skiers also had lower trabecular separation than swimmers and controls. Male alpine skiers had 20% higher trabecular bone mineral density than swimmers, and male soccer players exhibited 22% higher trabecular number than swimmers at the distal tibia (p<0.05). Male alpine skiers and soccer players had 28-38% higher failure load at the distal tibia than swimmers. No differences in bone parameters were observed between swimmers and controls for either sex at either site. Both muscle strength and sporting activity were predictors of failure load at the distal tibia in the female cohort. Sporting activity, but not muscle strength, was a significant predictor of failure load in the male cohort at both the radius and tibia. This data suggests that impact loading in sporting activity is highly associated with bone quality. Longitudinal and interventional studies are required to further clarify the muscle-bone interaction.

The Intrinsic Ferromagnetism in a MnO2 Monolayer.

The Mn atom, because of its special electronic configuration of 3d(5)4s(2), has been widely used as a dopant in various two-dimensional (2D) monolayers such as graphene, BN, silicene and transition metal dichalcogenides (TMDs). The distributions of doped Mn atoms in these systems are highly sensitive to the synthesis process and conditions, thus suffering from problems of low solubility and surface clustering. Here we show for the first time that the MnO2 monolayer, synthetized 10 years ago, where Mn ions are individually held at specific sites, exhibits intrinsic ferromagnetism with a Curie temperature of 140 K, comparable to the highest TC value achieved experimentally for Mn-doped GaAs. The well-defined atomic configuration and the intrinsic ferromagnetism of the MnO2 monolayer suggest that it is superior to other magnetic monolayer materials.

Genetic variants in IFIH1 play opposite roles in the pathogenesis of psoriasis and chronic periodontitis.

The IFIH1 gene is a key factor connecting environmental and genetic factors in the pathogenesis of immune-related diseases. We aimed to investigate whether it has effects on psoriasis, chronic periodontitis and skin test-positive penicillin allergy and to confirm whether these diseases have shared molecular mechanisms originating from shared genetics. Two common variants in IFIH1 were genotyped in 561 patients with psoriasis, 421 patients with chronic periodontitis, 175 patients with skin test-positive penicillin allergy and 1100 shared controls. Then, case-control study was used to analyse the association between IFIH1 and the three diseases. The allele distributions of rs1990760 and rs3747517 in the Chinese population are much different from the European population. The A allele of rs1990760 (OR = 1.30, P = 5.4 × 10(-3)) and A-G (rs1990760/rs3747517) haplotype (OR = 1.31, P = 3.8 × 10(-3)) were highly associated with the risk of psoriasis. However, the A allele of rs1990760 (OR = 0.73, P = 7.8 × 10(-3)) and A-G haplotype (OR = 0.71, P = 4.5 × 10(-3)) were identified as protective factors for chronic periodontitis. IFIH1 affects several immune-related diseases, including psoriasis and chronic periodontitis, and provides a molecular link between genetic susceptibility, viral infections and immune-related diseases. Moreover, we also confirm the hypothesis that shared molecular mechanisms from common genetic variants contribute to a spectrum of immune-related diseases.

The accuracy of dose calculations by anisotropic analytical algorithms for stereotactic radiotherapy in nasopharyngeal carcinoma.

Nasopharyngeal tumors are commonly treated with intensity-modulated radiotherapy techniques. For photon dose calculations, problems related to loss of lateral electronic equilibrium exist when small fields are used. The anisotropic analytical algorithm (AAA) implemented in Varian Eclipse was developed to replace the pencil beam convolution (PBC) algorithm for more accurate dose prediction in an inhomogeneous medium. The purpose of this study was to investigate the accuracy of the AAA for predicting interface doses for intensity-modulated stereotactic radiotherapy boost of nasopharyngeal tumors. The central axis depth dose data and dose profiles of phantoms with rectangular air cavities for small fields were measured using a 6 MV beam. In addition, the air-tissue interface doses from six different intensity-modulated stereotactic radiotherapy plans were measured in an anthropomorphic phantom. The nasopharyngeal region of the phantom was especially modified to simulate the air cavities of a typical patient. The measured data were compared to the data calculated by both the AAA and the PBC algorithm. When using single small fields in rectangular air cavity phantoms, both AAA and PBC overestimated the central axis dose at and beyond the first few millimeters of the air-water interface. Although the AAA performs better than the PBC algorithm, its calculated interface dose could still be more than three times that of the measured dose when a 2 × 2 cm(2) field was used. Testing of the algorithms using the anthropomorphic phantom showed that the maximum overestimation by the PBC algorithm was 20.7%, while that by the AAA was 8.3%. When multiple fields were used in a patient geometry, the dose prediction errors of the AAA would be substantially reduced compared with those from a single field. However, overestimation of more than 3% could still be found at some points at the air-tissue interface.

Two susceptible diabetogenic variants near/in MTNR1B are associated with fasting plasma glucose in a Han Chinese cohort.

AIMS: To investigate the two variants (rs1387153 and rs10830963) near/in the melatonin receptor 1B gene (MTNR1B) and to determine their association with Type 2 diabetes, as well as with the regulation of fasting plasma glucose (FPG) in Han Chinese subjects. METHODS: The two variants were genotyped in 1912 unrelated Type 2 diabetic patients and 2041 healthy individuals. Association with Type 2 diabetes was calculated by logistic regression with adjustments for sex, age and body mass index. The possible connection between the risk alleles and FPG was analysed by multiple linear regression. RESULTS: The two polymorphisms were associated with FPG levels in the healthy individuals (P = 0.003 and P = 0.002, respectively), and the G allele of rs10830963 was also associated with an increased risk of Type 2 diabetes in our patient sample (odds ratio, 1.12; 95% confidence interval, 1.02-1.23; P = 0.024). Moreover, the linkage disequilibrium degree of two single nucleotide polymorphisms was high (r(2) = 0.66), which is similar to that of Europeans. CONCLUSIONS: The common variant in MTNR1B confers the risk of Type 2 diabetes and modulates FPG in both the Han Chinese and European populations.

Ultraviolet B exposure of peripheral blood mononuclear cells of patients with systemic lupus erythematosus inhibits DNA methylation.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, in which sunlight (especially ultraviolet B (UVB) 290-320 nm) is known to induce exacerbation of disease. DNA methylation regulates gene expression, and hypomethylation is associated with abnormal cell function in SLE. The purpose of this study was to investigate the effect of UVB on DNA methylation in SLE and its significance in the pathogenesis of SLE. Forty-five patients with SLE and 20 healthy controls were enrolled in the study, which involved the investigation of DNA methylation and DNA methyltransferase 1 (DNMT1) of peripheral blood mononuclear cells with UVB irradiation. Our results demonstrate the following: The level of DNA methylation in patients with SLE was lower than that in the control group. DNA methylation was decreased after UVB irradiation at different dosages especially in patients with marlar rashes and leucopenia, but no significant difference was observed in the DNMT1 mRNA expression. DNA methylation levels in patients with active SLE were more sensitive to UVB. In conclusion, UVB exposure is able to inhibit DNA methylation, which subsequently takes part in the pathogenesis of SLE.

The possible significance of Clostridium spp. in blood cultures.

The significance of Clostridium spp. in blood cultures was evaluated by two methods. In the first part of the study, a group of 80 patients with Clostridium spp. bacteraemia was compared with a group of 100 patients with Bacillus spp. in blood cultures, making the assumption that Bacillus almost invariably represents contamination (pseudobacteraemia). Significant differences were found between the two groups, suggesting that growth of Clostridium did not represent pseudobacteraemia. Patients with Clostridium bacteraemia were older, had a higher frequency of gastrointestinal disease (especially colorectal tumours), were associated more frequently with polymicrobial bacteraemia, and had a higher mortality rate. In the second part of the study, each of the 80 cases of Clostridium bacteraemia was evaluated individually for clinical relevance by an infectious diseases expert. In two-thirds of the cases, isolates of Clostridium from blood were considered to be of clinical relevance, whereas in one-third of cases, the clinical significance of this finding was doubtful. It was concluded that growth of Clostridium spp. in blood cultures, even in the absence of one of the histotoxic syndromes, is often of clinical significance, and that such findings should be properly evaluated and not ignored.

Customization in a unified framework for summarizing medical literature.

OBJECTIVE: We present the summarization system in the PErsonalized Retrieval and Summarization of Images, Video and Language (PERSIVAL) medical digital library. Although we discuss the context of our summarization research within the PERSIVAL platform, the primary focus of this article is on strategies to define and generate customized summaries. METHODS AND MATERIAL: Our summarizer employs a unified user model to create a tailored summary of relevant documents for either a physician or lay person. The approach takes advantage of regularities in medical literature text structure and content to fulfill identified user needs. RESULTS: The resulting summaries combine both machine-generated text and extracted text that comes from multiple input documents. Customization includes both group-based modeling for two classes of users, physician and lay person, and individually driven models based on a patient record. CONCLUSIONS: Our research shows that customization is feasible in a medical digital library.

Measured versus estimated energy expenditure in mechanically ventilated critically ill patients.

Accurate determination of energy expenditure is essential in patients receiving nutritional support to meet metabolic needs. The purpose of this study was to assess and compare the energy expenditure as measured by indirect calorimetry (MEE) and estimated by 5 equations in the mechanically ventilated critically ill patients. Forty-six patients were divided into either enteral nutrition (EN) (n=l2), total parenteral nutrition (TPN) (n=16) or combined (EN plus TPN) (n=l8) groups. Patients' energy expenditure was measured by indirect calorimetry on two occasions. Anthropometric and biochemical measurements, energy expenditure and medical status (APACHE II score) were also assessed in the intensive care unit (ICU) of Taichung Veteran General hospital. No significant difference was found in the MEE among the 3 groups. The type of nutritional support did not affect MEE. Energy expenditure calculated by using Harris- Benedict, Kleiber and Liu equations times the estimated stress factor did not significantly different than the values of MEE in all groups. There were significant correlations (P<0.01) between MEE and patients' sex (r=-0.499), age (r=-0.402), height (r=0.533), knee height (r=0.431), current body weight (r=0.379), usual body weight (r=0.407), ideal body weight (r=0.466) and urinary urea nitrogen (r=0.383) in the pooled group. Results demonstrated that energy expenditure could be estimated in most critically ill patients by using Harris-Benedict, Kleiber and Liu equations if the estimated stress factor is in the reasonable value.

Vitamin B6 intakes and status of mechanically ventilated critically ill patients in Taiwan.

OBJECTIVE: To assess vitamin B6 intake and status of critically ill patients. The relationship between vitamin B6 status indicators and the severity of illness and outcome in these patients was also examined. DESIGN: Prospective clinical study. SETTING: The study was performed at the Taichung Veteran General Hospital, in the central part of Taiwan. SUBJECTS: Ninety-four patients in the intensive care unit (ICU) entered the study and 46 patients successfully completed this study. INTERVENTIONS: No intervention. MAIN OUTCOME MEASURES: Vitamin B6 intake was recorded for 14 days. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and urinary 4-pyridoxic acid (4-PA)) and indirect measures (erythrocyte alanine (EALT-AC) and aspartate (EAST-AC) aminotransaminase activity coefficient). The severity of illness (APACHE II score), the length of ventilation dependency, and the length of ICU and hospital stay were recorded. RESULTS: Patients had an adequate mean vitamin B6 intake (16.26+/-19.39 mg) during the 14 day study. Mean vitamin B6 intake was significantly higher on day 14 than on day 1 (P<0.001). However, plasma PLP and PL concentrations significantly decreased at the 14th day after admission (P<0.05). Erythrocyte alanine aminotransaminase activity coefficient and EAST-AC did not change significantly. Urinary 4-PA significantly increased at the 14th day (P<0.001). No significant relationships were found between APACHE II scores and clinical outcomes (the length of ICU and hospital stay, the length of ventilation dependency) of patients, vitamin B6 intake or status indicators. CONCLUSIONS: Critically ill patients received nutritional support in the ICU, and had sufficient mean vitamin B6 intake and adequate vitamin B6 status. Therefore, the severity of illness and the results should not be affected by vitamin B6 status. However, we have noted that plasma PLP and PL concentrations significantly decreased while vitamin B6 intake significantly increased on day 14. Critical clinical conditions and complex metabolism in the critically ill may account for the reduction of plasma PLP and PL. Since vitamin B6 deficiency causes profound effects on immune system function, dietary or supplemented vitamin B6 intake is suggested for hospitalized patients.

Structural basis for interaction of FGF-1, FGF-2, and FGF-7 with different heparan sulfate motifs.

Stromal cell-derived FGF-7 binds and activates only the resident FGFR2IIIb in epithelial cells while FGF-1 and FGF-2 exhibit a broader interaction with multiple isoforms of FGFR. Here we report the structure of FGF-7 that has been solved to 3.1 A resolution by molecular replacement with the structure of a dual function chimera of FGF-7 and FGF-1 (FGF-7/1) which was resolved to 2.3 A. Comparison of the FGF-7 structure to that of FGF-1 and FGF-2 revealed the strongly conserved Calpha backbone among the three FGF polypeptides and the surface hydrophobic patch that forms the primary receptor-binding domain. In contrast, a decrease and dispersion of the positive surface charge density characterized the heparin-binding domain of FGF-7 defined by homology to that of FGF-1 and FGF-2 in complexes with heparin. A simple heparin hexasaccharide that cocrystallized with FGF-1 and FGF-2 and protected both against protease in solution failed to exhibit the same properties with FGF-7. In contrast to FGF-1 and FGF-2, protection of FGF-7 was enhanced by heparin oligosaccharides of increased length with those exhibiting a 3-O-sulfate being the most effective. Protection of FGF-7 required interaction with specifically the fraction of crude heparin retained on antithrombin affinity columns. Conversely, heparin enriched by affinity for immobilized FGF-7 exhibited anti-factor Xa activity similar to that purified on an antithrombin affinity matrix. In contrast, an FGF-1 affinity matrix enriched the fraction of crude heparin with low anti-factor Xa activity. The results provide a structural basis to suggest that the unique FGF-7 heparin-binding (HB) domain underlies a specific restriction in respect to composition and length of the heparan sulfate motif that may impact specificity of localization, stability, and trafficking of FGF-7 in the microenvironment, and formation and activation of the FGFR2IIIb kinase signaling complex in epithelial cells.

Endocrine function and oocyte retrieval after autologous transplantation of ovarian cortical strips to the forearm.

CONTEXT: In reproductive-age women, one of the common adverse effects of chemotherapy and radiotherapy is premature ovarian failure. In addition, a significant number of women experience early menopause due to oophorectomy performed for benign indications. OBJECTIVE: To develop an ovarian transplantation technique to preserve endocrine function in women undergoing sterilizing radiotherapy and/or chemotherapy, or oophorectomy. DESIGN AND SETTING: Case study of 2 patients in New York who received autologous ovarian transplantation (patient A, November 1999; patient B, April 2000) to the forearm prior to pelvic radiotherapy or after oophorectomy. PARTICIPANTS: Patient A is a 35-year-old woman with stage IIIB squamous cell cervical carcinoma and patient B is a 37-year-old woman with recurrent benign ovarian serous cysts. MAIN OUTCOME MEASURES: Follicular development evident by ultrasound examination; cyclical production of estradiol and progesterone; restoration of serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels to nonmenopausal range; and disappearance of menopausal symptoms. RESULTS: Menopause was confirmed immediately after the transplantation in both patients by serum follicle-stimulating hormone measurements (patient A, 47 mIU/mL; patient B, 50.7 mIU/mL). In patient A, follicle development was noted by physical and ultrasound examinations approximately 10 weeks after the transplantation. The mean (SE) follicle-stimulating hormone and luteinizing hormone levels decreased to 8.6 (0.4) mIU/mL and 12.8 (0.8) mIU/mL, respectively. The peripheral estradiol levels showed cyclical variation (mean [SE], 115 [9.2] pg/mL [422 (33.8) pmol/L), and during the 18-month follow-up, a dominant follicle developed each month. The estradiol levels from the right cubital vein were consistent with ovarian vein measurements (mean [SE], 1069 [269] pg/mL [3924 (987.5) pmol/L]). Percutaneous oocyte aspirations yielded a mature oocyte. In patient B, ovarian function was demonstrated by ultrasound visualization of a 9-mm follicle by 6 months after transplantation. Thereafter, the patient had spontaneous menstruation every 25 to 28 days. Ovulation was further confirmed by midluteal progesterone measurements (range, 7-10.1 ng/mL; mean [SE], 8.5 [0.9] ng/mL). Patient B's ovarian graft was still functional 10 months after the transplantation. CONCLUSIONS: Subcutaneous ovarian transplantation appears to be a relatively simple, novel technique to preserve endocrine function in women undergoing sterilizing cancer therapy or surgery.

Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis.

We have reported that normal human salivary gland-derived epithelial cells exclusively express keratinocyte growth factor receptor (KGFR). In the process of malignant transformation of human salivary gland tumors, KGFR gene expression disappeared concomitantly with the de novo expression of the fibroblast growth factor receptor 1 (FGFR1) and FGFR4 genes. In the present study, we introduced wild-type KGFR cDNA or chimeric KGFR/FGFR1 cDNA, which encoded the extracellular domain of KGFR and the intracellular domain of FGFR1, into the HSY human salivary adenocarcinoma cell line. The KGFR tyrosine kinase suppressed the activity of FGF receptor substrate 2 (FRS2) and inhibited the growth of HSY by inducing differentiation and apoptosis in vitro and in vivo. Our results provided significant insight into the mechanism of KGFR tumor suppression and suggest that KGFR gene therapy might be a viable method of inhibiting human salivary adenocarcinoma growth.